Glaucoma is a blinding eye disease in which elevated intraocular pressure (IOP) produces optic nerve damage. There is a defect in the ability of aqueous humor to leave the eye in primary open-angle glaucoma (POAG) and also in steroid-glaucoma, presumably at the level of the trabecular meshwork (TM) outflow pathway, but the pathogenic mechanisms involved in these conditions have not been explained. We are investigating these questions using an in vitro model system in which human TM cells are grown in tissue culture and exposed to prolonged dexamethasone (DEX), at a concentration which reaches the anterior chamber, followed by an investigation into the changes which occur in protein synthesis using biochemical, cellular, and molecular biological assays. Our findings demonstrate major progressive new inductions at both the mRNA and protein/glycoprotein levels. The magnitude of the changes as well as correlations with IOP changes in the dose-response and time course of the DEX inductions suggest that these studies may provide information relevant to clinical and biological effects. We are currently exploring the synthesis, processing, transport, and localization as well as the biological properties of the induced proteins and glycoproteins (of which one major induction appears to be coded for by a unique cDNA) as possible clues to steroid-induced elevation of IOP and glaucoma.